Abstract
Background:Bone marrow myelofibrosis (BMF) that develop on top of Polycythaemia vera (PV) and essential thrombocythemia leads to shortening of the patient’s overall survival. This study aimed to address the impact of miR-146a rs2431697 polymorphism on inflammatory biomarkers and genes expression and the hazards of myelofibrosis progression. Patients and Methods:The study included 88 myeloproliferative neoplasm (40 PV; 27 ET; 21 MF) and 90 healthy controls. For all investigated subjects miR-146a rs2431697 genotypes were identified by sequencing and the expression of miR-146a; IL-1β; NF-κB; a NOD-like receptor family, pyrin domain containing 3 (NLRP3) genes were estimated by real time PCR. Results:miR146a genotypes revealed that there was significant association between TT and TC genotypes with MF. The degree of miR146a expression was significantly reduced in MF as compared to both PV and ET. In contrast; the levels of IL-1β; NF-κB; NLRP3 genes expression were significantly elevated in MF patients group as compared to PV and ET patients’ group. Multivariate analysis identified TT genotype as poor predictor of MF progression. Conclusion:miR-146a rs2431697 TT genotype is associated with high risk of MF progression in MPN patients. Targeting of IL-1β; NF-κB; NLRP3 genes might help in hindering of MF progression in MPN patients,
Highlights
The Philadelphia negative Myeloproliferative neoplasms (MPNs) (BCR-ABL-ve MPNs) are the most frequent diseases among the myeloproliferative disorders
During the progressive course of Polycythaemia vera (PV) and essential thrombocytosis (ET); some of the patients transformed into MF which usually associated with complications namely thrombosis, hemorrhages, and worse complication which is transformation to acute myeloid leukemia (AML) (Vainchenker and Kralovics, 2017)
All patients diagnosed as MPN who presented at Mansoura University Oncology Center (MUOC) between January 2015 up to September 2020 were included in cohort prospective study
Summary
The Philadelphia negative Myeloproliferative neoplasms (MPNs) (BCR-ABL-ve MPNs) are the most frequent diseases among the myeloproliferative disorders. MPNs are subcategorized into 3 subtypes that include polycythemia Vera (PV), essential thrombocytosis (ET), and Myelofibrosis (MF). This study aimed to address the impact of miR146a rs2431697 polymorphism on inflammatory biomarkers and genes expression and the hazards of myelofibrosis progression. The degree of miR146a expression was significantly reduced in MF as compared to both PV and ET. In contrast; the levels of IL-1β; NF-κB; NLRP3 genes expression were significantly elevated in MF patients group as compared to PV and ET patients’ group. Conclusion: miR-146a rs2431697 TT genotype is associated with high risk of MF progression in MPN patients. Targeting of IL-1β; NF-κB; NLRP3 genes might help in hindering of MF progression in MPN patients, Keywords: miR-146a- IL-1β- NF-κB- NLRP3- MPN- Myelofibrosis
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